Fesoterodine is [2-[(1R)-3-(Di(propan-2-yl)amino)-1-phenylpropyl]-4-(hydroxymethyl) phenyl]2-methylpropanoate and represented by formula (I).

The product is marketed in the form of Fumarate salt. The current pharmaceutical product containing this drug is being sold by Pfizer using the trade name Toviaz, in the form of extended release oral tablets. Fesoterodine is cholinergic antagonist and muscarinic antagonist. Fesoterodine is rapidly de-esterified to its active metabolite, (R)-2-(3-diisopropylamino-1-phenylpropyl)-4-hydroxymethyl-phenol, or 5-hydroxy methyl tolterodine, which is a muscarinic receptor antagonist. Fesoterodine is used as Urinary Incontinence Products. It is used to treat overactive bladder.
Few processes for the synthesis of 3,3-diphenylpropylamine derivatives have been described in the literature.
Tolterodine and other 3,3-diphenylpropylamine analogs were first described in U.S. Pat. No. 5,382,660. Said patent described several methods for preparing tolterodine and its analogs generally based a process for the preparation of Tolterodine.
U.S. Pat. No. 6,713,464 disclosed a variety of 3,3-diphenylpropylamine derivatives, processes for their preparation, pharmaceutical compositions in which they are present and method of use thereof.
Fesoterodine obtained by the processes described in the above prior art does not have satisfactory purify for pharmaceutical use.
In order to secure marketing approval for a new drug, product, a drugs manufacturer must submit detailed evidence to the appropriate regulatory authority to show that the product is suitable for release on to the market. The regulatory authority must be satisfied, inter alia, that the active agent is acceptable for administration to humans and that the particular formulation which is to be marketed is free from impurities at the time of release and has an appropriate shelf-life.
Submissions made to regulatory authorities therefore typically include analytical data which demonstrate (a) that impurities are absent from the drug at the time of manufacture, or are present only at a negligible level, and (b) that the storage stability, i.e. shelf life, of the drug is acceptable. These data are usually obtained by testing the drug against an external standard, or reference marker, which is a suitably pure sample of a potential impurity or a potential degradation product.
Potential impurities in pharmaceutically active agents and formulations containing them include residual amounts of synthetic precursors to the active, agent, by-products which arise during synthesis of the active agent, residual solvent, isomers of the active agent, contaminants which were present in materials used in the synthesis of the active agent or in the preparation of the pharmaceutical formulation, and unidentified adventitious substances. Other impurities which may appear on storage include substances resulting from degradation of the active agent, for instance by oxidation, or hydrolysis.
In general, the chemical purity of the Active Pharmaceutical Ingredient (API) produced in an industrial scale is one of the critical parameters for its commercialization. The American Food and Drug Administration (FDA) as well as European authorities for drug control require API's to be free of impurities to the maximum possible extent in accordance with the instruction Q7A of ICH (International Conference on Harmonization). The purpose is to achieve maximum safety of use of the medicament in the clinical practice. National administration and control authorities usually require the content of an individual impurity in the API not to exceed the limit of 0.1%. All substances (generally referred to as impurities) contained in the API in a quantity exceeding 0.1% should be isolated and characterized in accordance with ICH recommendations. Nevertheless, the content of substances with a known structure (isolated and characterized) in a pharmaceutically acceptable ingredient should not exceed the limit of 0.15%.
The process of preparation of a pharmaceutically acceptable ingredient as well as the resulting quality of the ingredient must be under strict control in accordance with the principles of the Good Production Practice. For this control an array of methods of analytic chemistry are used among which separation, techniques allowing very sensitive analyzing of the ingredient as well as its mixtures with other substances occupy a prominent position. High Performance Liquid Chromatography (HPLC), ultra-high performance liquid chromatography (UPLC) or Gas Chromatography (GC) is usually used for this purpose.
Impurities present in the API are then determined by the relative position, of the peak in the HPLC or GC chromatogram while the peak position is usually expressed as the time (in minutes) necessary for the imparity to travel from the point of sample injection to the HPLC or GC column filled with a suitable sorbent to the detection place. The time necessary for a chemical substance (e.g. API or impurity) to get from the injection, point to the detector under standard conditions is referred to as the “retention time”, Retention times (RT) related to the retention-time of a standard (usually RT of the API) are called “relative, retention times”. The relative retention time (RRT) of the API usually, takes the value 1, components that need a shorter time to travel to the detector manifest lower relative retention times than 1 while components travelling more slowly exhibit higher relative retention, times than 1. Under standard conditions the relative retention times are considered, as standard characteristics of the analyzed substance, i.e. they only depend on the chemical structure of the particular constituent. The position of the peak in the chromatogram, or the retention time, is only a quality parameter that does not provide information about the quantity of the analyzed substance.
For reliable determination of the content of the analyzed constituent it is necessary to have an analytical standard of the substance. The result of the quantity determination is usually expressed in percent by weight. If standards of impurities (including raw materials, intermediate products and optic isomers) are not available, it is very difficult to determine their actual content in the API, to find an acceptable analytic method and to perform its validation. Without, the possibility of reliable quality assurance of the API it is not possible to control the process of its production, and use the obtained, substance for the preparation of a pharmaceutical formulation.
Standards of impurities, analytic methods of chemical purity of the API and quantity determination methods are extremely important for the control of the production process and consequently for successful commercialization of the product.
The solution presented by us represents a new and convenient method of determining chemically pure Fesoterodine (I), including methods of analytical control of the production process and quality of the target substance. Also provides the packaging condition that improves its stability.